Speaker: Sarah Arron, MD, PhD, Dermatologic Surgeon
Sarah Arron, MD, PhD: Hello, my name is Sarah Arron and I'm a Mohs micrographic surgeon in Burlingame, California. On behalf of my colleagues, I'm delighted to share our recent publication, "Association of a 40-Gene Expression Profile With Risk of Metastatic Disease Progression of Cutaneous Squamous Cell Carcinoma and Specification of Benefit of Adjuvant Radiation Therapy." The criteria for recommending adjuvant radiation for cutaneous squamous cell carcinoma encompass many high-risk clinicopathologic features. However, their effectiveness in predicting ART benefit has not been consistently demonstrated, and consequently, a broad and inconsistent spectrum of patients is referred for ART with only a subset benefiting. The 40-gene expression profile test was developed to stratify risk of metastasis for patients with primary high risk cS- CC who have one or more clinicopathologic risk factors. Tumors are classified as low risk (Class 1), high risk (Class 2A), and very high risk (Class 2B) with overall metastasis rates of 6.5%, 19.4% and 45.9% respectively. This biologic risk predictor is independent of clinicopathologic staging and studies have shown that the 40- GEP test offers independent prognostic value when combined with current risk assessment methods and can positively influence treatment decisions for cS- CC patients. The testing criteria for 40-GEP overlap significantly with NCCN, ACR, and ASTRO guidelines for ART consideration. This study aimed to determine whether the 40-GEP test could identify patients most likely to benefit from ART in reducing nodal or distant metastasis. Eligible patients were drawn from two merged validation cohorts. Patients were followed for at least three years or until a nodal or distant metastatic event occurred. Clinicians and patients were naive to GEP result at the time of clinical decision making. Patients were excluded if ART status was unknown, occurred after metastatic event or if a nodal event was reported within three months of diagnosis. 920 patients were eligible for analysis. To control for the variety of patient and tumor characteristics and treatment selection bias, randomly sampled pairs of matched ART and non-ART treated patients comprising 10,000 bootstrap resampled cohorts were each analyzed for 5-year metastasis- free survival and predicted time to metastasis. Of 96 patients with local recurrence, 56.3% developed metastases, and of these 88.9% had a local recurrence before or concurrently with metastatic event. After matching for clinicopathological risk, median 5-year progression rates for resampled cohorts showed approximately 50% improvement in Class 2B ART-treated as compared to untreated cohorts. Class 2B ART-treated cohorts had a 5-fold delay in predicted time to metastatic event and deceleration of disease progression Compared to ART untreated cohorts. Extensive control analysis demonstrated the robustness of the results by systematically dropping one risk factor from propensity matching and then retesting for ART benefit. The 40-GEP Class 2B result was the only risk factor that successfully identified patients benefiting from ART. And while our propensity matching was based on individual risk factors, we also tested whether summary staging or NCCN risk assessment could identify patients benefiting from radiation, but did not find significant results. We conclude that the 40-GEP identifies patients at highest risk for nodal or distant metastasis who may derive the greatest benefit from ART, as well as patients who may have clinical indications for ART but are at lower biologic risk of metastasis. Integration of 40-GEP testing into current guidelines improves precision concerning the benefit of ART in individual patients, and can help dermatologists and radiation oncologists in evaluating the risks and benefits of ART in a high-risk cutaneous squamous cell carcinoma.
